1. Design and synthesis of naphthalenic derivatives as new ligands at the melatonin binding site MT3.
- Author
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Leclerc V, Ettaoussi M, Rami M, Farce A, Boutin JA, Delagrange P, Caignard DH, Renard P, Berthelot P, and Yous S
- Subjects
- Binding Sites drug effects, Ligands, Molecular Structure, Naphthalenes chemical synthesis, Naphthalenes chemistry, Receptors, Melatonin chemistry, Stereoisomerism, Structure-Activity Relationship, Drug Design, Melatonin chemistry, Naphthalenes pharmacology, Receptors, Melatonin metabolism
- Abstract
Naphthalenic analogs of MCA-NAT (5-methoxycarbonylamino-N-acetyltryptamine) have been synthesized and evaluated as melatonin receptor ligands. Introduction of a methoxycarbonylamino substituent at the C-7 position of the naphthalenic nucleus yields MT3 selective ligands. This selectivity can be modulated with suitable variations of the C-7 position and the acyl group on the C-1 side chain. We identified new series of compounds with affinity for the MT3 binding site in the nanomolar range, and singled out a selective ligand, (N-[2-(7-methylsulfamoyl-naphth-1-yl)ethyl]acetamide (17), with a Ki of 4.9 nM and selectivity of 1024 and 2040 versus MT1 and MT2 receptors respectively., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)
- Published
- 2011
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